The research goal is to learn how birds and mammals differ in their tolerance of extreme hypoxia. At 10 km above sea level, birds maintain metabolism, whereas white rats become comatose at 6.5 km. Hemorrhaged pigeons replace blood with interstitial fluid, becoming extremely anemic, yet their vital signs remain normal; white rats undergo shock and die. Few adaptations have been found to explain birds' greater hypoxia endurance. The specific aim is therefore to test the hypothesis that avian adaptations to hypoxia at the cellular level permit normal cell function, and that corresponding adaptations are deficient in mammals. Rats and pigeons will undergo tissue hypoxia by ischemia, hemorrhage, or exposure to hypoxic air. Blood flow, temperature, and PO2 will be monitored in brain, heart, and skeletal muscle. Also measured will be blood pressure, blood gases and pH, body fluid distribution, and maze learning and memory. Tissue and cell changes measured include enzyme activities, ATP/ADP, and concentrations of metabolic intermediates and metabolites. The elucidation of cellular hypoxia-tolerance mechanisms in birds has biomedical relevance in hemorrhage and shock, stroke, coronary blockage, and altitude sickness. Bird adaptations may even suggest means to improve mammal hypoxia tolerance. The research will meet MBRS objectives by being subdivided into student projects that test subsidiary hypotheses. During an initial period of reading and tutorials with the PI, students will learn about problems and methods, then with the PI's aid and encouragement will formulate hypotheses, design experiments, do surgery and other preparations, acquire and analyze data, and interpret results, gaining experience with modern instruments and techniques. They will present results at laboratory meetings, departmental symposia, and scientific conferences, and as publications in peer-reviewed journals.